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E A Porta

Publications and source records attributed to E A Porta.

At least 19 recordsLinked to original sources

Effects of lovastatin and leupeptin on ceroidogenesis of vitamin E-deficient and -supplemented young rats.

Previous studies in young normal rats have shown that intracerebral administration of the proteinase inhibitor, leupeptin, caused a rapid accumulation of lipofuscin-like pigment in lysosomes of brain cells (Ivy et al., 1984a). On the other hand, we have recently found that the administration of lovastatin, an inhibitor of HMG-CoA reductase, reduced the ceroid-like pigment and dolichol contents in the crushed epididymal fat pad of rats (Porta et al., 1988). In order to study now the possible modulating effects of these enzyme inhibitors on ceroidogenesis associated with vitamin E deficiency, two main groups of weanling Wistar female rats were respectively fed ad libitum a vitamin E-deficient basal diet, or the same diet supplemented with 16 mg% of dl-alpha-tocopherol acetate. The vitamin E-deficient and -supplemented rats were further subdivided and received for 8 weeks their diets alone or with 2, 1, or 0.5 g of lovastatin/kg of diet. Other subgroups were treated with constant peritoneal infusion of 0.5 mg/day of leupeptin by means of osmotic minipumps (Alzet 2002) consecutively implanted at days 15, 30, and 45. Lovastatin treatment to vitamin E-deficient rats was associated with dose-dependent toxicity, resulting in 100%, 75%, and 50% mortality at concentrations of 2, 1, and 0.5 g/kg diet, respectively. This mortality was mainly due to extensive hepatic necrosis. Food intake and growth rates were reduced, while the relative weights of liver, kidneys, spleen, heart and brain, as well as the serum levels of GPT and GOT were significantly increased over the values of the untreated vitamin E-deficient control rats. The volumetric densities of ceroid pigment and the dolichol contents in liver and kidneys were not significantly modified. Lovastatin toxicity was partially prevented by vitamin E supplementation. However, in these supplemented rats, lovastatin treatment did not modify the volumetric densities of hepatic and renal ceroid, although the contents of hepatic and renal dolichol were significantly increased. No correlations could be found between levels of hepatic or renal ceroid and total dolichol content in vitamin E-deficient and supplemented rats. Leupeptin treatment to vitamin E-deficient rats only slightly reduced food intake and growth rates, and did not significantly modify the relative organ weights or the serum levels of cholesterol, GOT and GPT. Although in both vitamin E-deficient and -supplemented rats the leupeptin treatment consistently showed a tendency to increase the volumetric densities of hepatic and renal ceroid pigment, the differences with the control untreated rats were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase

Evaluation of the effect of glucan on hepatic, renal and mammary tumorigenesis in rats.

Glucan was evaluated for its ability to modify the hepatic and renal tumorigenesis induced in partially hepatectomized Sprague-Dawley female rats by diethylnitrosamine (DEN) and phenobarbital (PB), and the mammary tumorigenesis induced in intact Sprague-Dawley female rats by N-nitrosomethylurea (NMU). In both models the rats received every two weeks i.v. glucan (10 mg/kg) or equivalent amounts of dextrose. The results indicated that glucan did not significantly modify the incidence of the chemically-induced hepatic, renal and mammary tumors.

Animals

Effects of selenium supplementation on hepatocarcinogenesis in rats.

Four groups of weanling male Wistar rats (Groups A-D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast-based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair-feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.

Animals

Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. III. Biochemical and morphometric parameters of the liver.

The purpose of this study was to explore in rats the possible influence of the type of dietary fat at two extreme levels of vitamin E on several biochemically determined hepatic changes and on a number of quantitatively analyzed structural and ultrastructural variations with age in hepatic cells. Six groups of weanling Wistar male rats were fed ad libitum isoenergetic diets containing similar amounts (15 g per 100 g diet) of saturated fat (coconut oil), unsaturated fat (safflower oil) or a combination of both at two levels of dl-alpha-tocopherol (2 or 200 mg per 100 g of diet). Determinations were performed in rats killed at 3, 6, 12, 18 and 24 months. Although in relation to age and irrespective of the type of diet, several of the biochemical parameters fluctuated with time, comparisons of the results between the youngest and oldest rats showed no changes in the levels of hepatic RNA, phospholipids, cholesterol, total tocopherols and total collagens, significant increases in DNA and triglycerides and a significant decrease in total protein. While the type of diet did not have in general significant influences on the levels of DNA, RNA, total protein and collagens, either the type of dietary fat and/or the levels of vitamin E had some definite effects on the levels of triglycerides, cholesterol, phospholipids and total tocopherols, as well as on the in vitro formation of malonaldehyde and on the eventual occurrence of in vivo lipoperoxidation (diene conjugation). These effects, however, varied in relation to the duration of the diverse dietary treatments. The morphologic studies indicated that all the livers had variable but generally moderate degrees of fatty changes (mainly due to triglyceride accumulation) which were attributed to the moderate obesity found in the rats. The mean nuclear and cell dimensions of hepatocytes, the number of binucleated hepatocytes, surface density of rough endoplasmic reticulum, numerical density of mitochondria and the fractional cytoplasmic volume occupied by lipofuscin pigment in hepatocytes were not significantly affected by the type of diet, by age or by the eventual occurrence of in vivo hepatic lipoperoxidation, whereas the numerical density of hepatocytes (mono- and binucleated) and "litoral cells" (endothelial, Kupffer and Ito cells), although unaffected by diet, significantly increased with age. On the other hand, the fractional volume of mitochondria and peroxisomes, as well as the numerical density of peroxisomes, were significantly influenced by the type of dietary fat and to lesser extent by the dietary levels of vitamin E.

Aging

The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: appendix III. evaluation of viscera and other tissues.

Histopathological findings in the lungs, livers, bone marrows, small intestines, gonads, kidneys, and other tissues of the four pocket mice (Perognathus longimembris) that survived the Apollo XVII flight were evaluated in the light of their immediate environment and as targest of HZE cosmic ray particles. Results of this study failed to disclose changes that could be ascribed to the HZE particle radiation. Decreased numbers of erythropoietic cells in the bone marrow of the flight mice were probably related to the increased oxygen pressure. The small intestine showed no changes. Ovaries and tests appeared normal. Two of the three surviving male flight mice displayed early stages of spermatogenesis, just as ground-based controls did at the same season. Abnormalities were also not found in the thyroid, parathyroids, adrenals, or kidneys. The status of the juxtaglomerular apparatus could not be evaluated. The lungs exhibited nonspecific slight rections. A variety of incidental lesions were noted in the livers of both the flight mice and their controls. The heart muscle showed nothing that could be regarded as pathological. Sections of skeletal muscle examined were free from significant change.

Adrenal Cortex

Lysosomes in the pathogenesis of the renal necrosis of choline-deficient rats.

Previously published data from our laboratories led us to postulate that alterations in lysosomes may play a cardinal pathogenic role in the fatal renal necrosis of choline-deficient weanling rats. To explore this hypothesis further a series of five different experiments were carried out. In the first two experiments the effect of a "stabilizer" of the lysosomes, hydrocortisone, was studied; conversely, in the third and fourth experiments, the effect of a "labilizer," vitamin A, was studied. Finally, in the fifth experiment, the renal levels of a lysosomal enzyme, acid phosphatase, were evaluated biochemically. Results of the first two experiments revealed a protective effect of hydrocortisone while those of the third and fourth an aggravating effect of vitamin A. Results of the fifth experiment indicated lysosomal changes in the prenecrotic and early necrotic stages. These results along with those from our previous studies, support the concept that lysosomal alterations play an important pathogenic role in renal changes of choline-deficient weanling rats.

Acid Phosphatase